Biology is increasingly becoming an information-driven science. There is an enormous demand for biologists who are trained in mathematics and computer science and can think quantitatively. However, current disciplinary graduate training programs are not designed to accommodate these rapid changes in the biological research perspective. This need serves as the motivation for the development of specialized graduate training programs that will train students at the interface between biology, engineering and computer science. To address this need, UCSD initiated an interdisciplinary Graduate Program in Bioinformatics in 2000. The primary objectives in this renewal application of the training grant are to continue the premier program, support the highest quality students and train them in a truly interdisciplinary paradigm blending biomedicine, computer science and engineering. The Program will continue to offer a core curriculum in Bioinformatics and a host of electives that will prepare a student solve difficult problems in biomedical research. Given the extraordinary number and quality of applicants, this application seeks to enhance the number of trainee slots to 15. Each trainee will continue to be funded for three years. The proposed Bioinformatics Graduate Training Program will train students through specialized courses and highly interdisciplinary research programs across eight departments: Bioengineering, Biological Sciences, Biomedical Sciences, Cell and Molecular Medicine, Chemistry and Biochemistry, Computer Science, Mathematics and Physics. Several participating faculty members in the program work on research problems of immediate and long term relevance to human health and medicine. Understanding transcriptional processes quantitatively - a problem highly relevant to regenerative medicine and to diseases such as cancer, mapping the biochemical networks involved in insulin resistance - a problem of fundamental interest to a host of diseases, predicting outcomes in cardiac activity in normal and pathological states, and studying inflammation and accompanying immune responses are some of the significant research problems that will form research topics for trainees in the UCSD Bioinformatics Program.